Fused Heterocyclic Compounds

Structure of Cgo and a carbon nanotube. Each carbon in Cgo is a bridgehead carbon for a five-membered ring and two six-membered rings. A nanotube is a cylinder composed of aromatic six-membered rings similar to graphite. The end of the tube is half of a Ceo sphere. Notice how the five-membered rings cause the structure to curve at the end of the tube. 

Purine is one of many fused heterocyclic compounds whose rings share two atoms and 16-12 

---

A fused heterocyclic compound (146) distantly related to the antiinflammatory agent cintazone (Chapter 12), which itself can be viewed as a cyclized derivative of phenylbutazone, retains the activity of the prototype, in the synthesis of 146, reaction of the nitroaniline 139 with phosgene gives intermediate 140, which is then reacted with ammonia to afford the substituted urea (141). Cyclization of the ortho nitrourea function by means of sodium hydroxide leads to the N-oxide (142) this last reaction represents... 

The synthesis of (5 5 5) fused heterocyclic compounds 7 <2001JOC412> has been achieved in 84% yield via annulation of internal alkynes by imines 287 derived from o-iodoaniline in the presence of palladium catalyst (Scheme 51). 

Diaminofurazans 156 are useful starting materials for the synthesis of fused heterocyclic compounds. For example, 3,4-diaminofurazans 156 reacted with dicarbonyl compounds (e.g., with ct-keto acids) to produce a series of 5-hydroxy[l,2,5]oxadiazolo[3,4-A pyrazines 163 (Equation 26) <2003BML3133>. 

The fused heterocyclic compounds 276 containing furazan fragment were prepared by reaction of the annelated 2,3-dichloropyrazines with malononitrile, followed by treatment with RH <2001MC152>. 

Intramolecular oxidation of /V-alkyl-/V -heteroarylthioureas provides a synthetic pathway to fused heterocyclic compounds (Scheme 63).149... 

Benzonitrile oxide and mesitonitrile oxide undergo 1,3-dipolar cycloaddition reactions with 1,3,5-triphosphinines under mild conditions to afford fused heterocyclic compounds (Scheme 1.33), for example, 192 and 193. Oxaphosphazoles and oxadiphospholes have become accessible by thermal fragmentation reactions of such fused heterocyclic compounds (358). 

Pyrido[2,3- pyrimidine bicyclic systems represent interesting fused heterocyclic compounds having pharmacological and biological properties. Their syntheses are well documented in the literature. The pyridine or pyrimidine rings have been used as precursors for constructing the second heterocyclic ring. 

This chapter is the second of a three-part series reviewing halogenation of aromatic heterocycles. Part 1 [93AHC(57)291] described halogenation methods and their application to five-membered systems. Part 3 will cover the benz and other fused heterocyclic compounds. Material published since 1978 is emphasized, although earlier references are included where... 

Fused heterocyclic compounds are similar to polycyclic aromatic compounds except that one or more of the fused rings is a heterocycle. Explain whether or not the heterocyclic rings of these compounds are aromatic. 

Polynuclear Aromatic Hydrocarbons 735 16-11 Aromatic Allotropes of Carbon 737 16-12 Fused Heterocyclic Compounds 739 16-13 Nomenclature of Benzene Derivatives 740... 

Purine is one of many fused heterocyclic compounds whose rings share two atoms and the bond between them. For example, the following compounds all contain fused heterocyclic aromatic rings ... 

The properties of fused-ring heterocycles are generally similar to those of the simple heterocycles. Fused heterocyclic compounds are common in nature, and they are also used as drugs to treat a wide variety of illnesses. Figure 16-17 shows some fused heterocycles that occur naturally or are synthesized for use as drugs. 

Recognize fused aromatic systems such as polynuclear aromatic hydrocarbons and fused heterocyclic compounds, and use the theory of aromatic compounds to explain their properties. 

An interesting new application of enaminone chemistry is ring closure involving benzyne intermediates. In this way an intramolecular arylation of enaminones is effected. The method is used for the synthesis of fused heterocyclic compounds and natural products119-121. Phenanthridone derivatives can be obtained in good yield119. 

A nonconcerted mechanism of the 3-aza-Cope rearrangement of the enammonium salts has also been proposed by Mariano and coworkers 116a,ft, although the charge-accelerated rearrangements so far discussed proceed via the pericyclic route. The zwitterionic 7V-vinylisoquinuclidines formed from substrates 173 and a propiolate ester rearrange to fused heterocyclic compounds 174 through a stepwise pathway (Scheme... 

In an attempted synthesis of the spiro compounds 123 from the cyclic 1,1-enediamines 122 derived from cyclic ketones, in contrast to the expectation, the cyclic ketone ring is cleaved under mild reaction conditions and fused heterocyclic compounds 124 are obtained in good yields from 122 and ethyl propiolate (equation 43)58,122. 

Diphenylcyclopropenone (194) reacts with nitro-substituted 1,1-enediamines 7 in the presence of K2C03 to give a fused heterocyclic compound 195155 (equation 80). 

A number of unusually fused heterocyclic compounds have been reported by Tu and co-workers [118]. The three-component domino reaction of an aldehyde, an enaminone 72 and malononitrile resulted in the formation of polysubstituted imi-dazo[l,2-a]quinazolines 73 and pyrimido[l,2-a]quinolines 74. (Scheme 56) When enaminone 75 was reacted using the same reaction conditions, this resulted in the formation of quinolino[l,2-a]quinazolines 76 in good yields. In this one-pot reaction, up to five new bonds were formed accompanied by the generation of the lactam group. Interestingly, the volume of ethylene glycol used seems to influence the yield of the product (Scheme 57). 

The diazotization of aromatic amines with a nucleophilic substituent at the ortho position is a common method of synthesis of benzo-fused heterocyclic compounds with two or more contiguous nitrogen atoms. Benzotriazoles (9), benzotriazinones (10), and benzothiadiazoles (11) are examples of heterocyclic ring systems that can be prepared in this way. 

Fujita, T., Wada, K., and Fujiwara. T., Preparation of substituted fused heterocyclic compounds as pharmaceuticals, Sankyo, Int. Patent Appl. WO 9918081, 1999 Chem. Abstr, 130, 296681, 1999. 

Oxygen and nitrogen nucleophiles add to diethyl l-(ethoxycarbonyl)vinylphosphonate to generate the formation of various fused heterocyclic compounds. Thus, A -carbapcncrns are readily prepared by the Michael addition of A-lithio-4-vinylazetidin-2-one to diethyl l-(ethoxycarbo-nyl)vinylphosphonate followed by ozonolysis of the adduct and subsequent treatment of the generated aldehyde by intramolecular Homer Wadsworth-Emmons reaction (Scheme 8.28). ... 

Nonetheless no treatise or monograph on the chemistry of heterocycles contains a mention, let alone an entire chapter, on peri-fused heterocyclic compounds as independent objects worthy of special consideration, equal to those of heteromonocyclic and ortho-fused substances. The previously published chapter (90AHC(51)l) and present review attempts to remedy this situation. 

An alternate approach to the fused heterocyclic compounds is the intramolecular cyclisation at an aromatic position. The Bischler-Napieralski reaction for the synthesis of the isoquinoline ring system illustrates this approach. 

In general, three approaches are possible for the synthesis of fused heterocyclic compounds. 

Various 2-amino-3-cyano-4//-pyrans have been observed to react with arylidene malonitriles and related derivatives to afford new fused heterocyclic compounds. The structure for a product from AH-pyran... 

---